6.8. Conclusions. References

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part II. Cancer stem cells


EMT is a critical cellular programme in normal development that is co-opted by epithelial cancer cells and is required for progression along the metastasis cascade. It provides cancer cells with mesenchymal traits critical for metastatic processes, including invasion, dissemination and colonization. The activation of EMT in epithelial cancers requires induction by stimuli present within the tumour microenvironment, subsequent activation of intracellular signalling networks and the stimulation of core transcription factors that orchestrate the regulation of many effector molecules involved in the processes of cell adhesion, mesenchymal differentiation, migration and invasion. The concept of epithelial – mesenchymal plasticity encompasses the adaptive changes that cancer cells can undergo along the EMT – MET axis and defines the high degree of flexibility that cancer cells exhibit between the epithelial and mesenchymal states. This cellular plasticity is evident in the strong association between cells that have undergone EMT and CSCs, a subpopulation of cancer cells capable of self-renewal that is an important contributor to tumour recurrence and metastasis. Hypoxia, a microenvironmental condition prominent in many solid tumours, induces EMT and is important for the regulation of CSCs and cancer cell metastasis. Finally, EMT plays an important role in the acquisition of treatment resistance, a situation that leads to tumour recurrence and metastasis and involves cancer cells with CSC properties. Therefore, targeting of cancer cells that have undergone EMT represents an important therapeutic avenue for the control and potential elimination of metastatic disease.

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